The purpose of this proposal is to study local regulatory mechanisms in the microcirculation. In keeping with the long term goals of this research grant, we plan to examine further the mechanism of the myogenic response of arterioles, specifically testing the hypothesis that wall tension (or stress) is the regulated variable. We will also examine the behavior of the arteriolar network during pressure alteration to determine whether pressure in the distal arterioles is regulated when large artery pressure is altered, as we have proposed. We will use isolated or exteriorized preparations of cat mesentery and cat sartorius muscle for these studies, measuring arteriolar diameter, dual slit velocity and microvessel intravascular pressure. The relative contributions of metabolic and myogenic factors in these two beds appear to be quite different. A study of behavior of the two preparations exposed to similar perturbations should provide information on the two mechanisms themselves and on the manner in which they interact. In addition, we will continue our studies of the venular network in skeletal muscle during changes in large artery pressure and during hyperemia. We propose that recruitment or curtailment of venules with flow and changes in apparent blood viscosity in the venules will tend to maintain a constant pressure drop across the venous network when flow changes. These data will be processed, stored and analyzed with the aid of electronic devices and computer programs developed in our laboratory. To obtain further information on the red cell velocity profile in the venular network we plan to use fluorescent-tagged red cells to time the passage of cells located at different distances from the vessel wall. The proposed research provides information of interest in ischemic disease, shock, portal hypertension and other states in which blood flow and intravascular pressure are altered from normal levels.